Interdisciplinarity to tackle the world's leading cause of death

What does it mean to advance science?

• 2.000.000 million scientific papers each year
• 30.000 scientific journals

Too many scientific papers...

Publishing papers is necessary:

• Grants, positions, promotions, status...  
                                 

This could lead to:

• fractioning (“salami slicing” data sets to the smallest publishable unit)
• surreptitiously re-using data in multiple publications
• duplicating papers
• publishing results that are preliminary or incomplete
• underemphasizing limitations
• making exaggerated claims
• data fabrication, falsification and plagiarism

Too many scientific papers...

Replication crisis:

• Amgen, a US biotech company:
  replicate 11% of 53 high-impact cancer research studies
• German pharmaceutical company Bayer:
  replicate 36% of 64 studies.
• John Ioannidis, MD, Professor of Medicine  and Statistics at Stanford University:
  replicate 44% of 45 of the most influential clinical studies

How to make sure your research is reproducible?

Too many scientific papers...

What happens with your results after they get published?

• Maybe you have written code, a thesis manuscript but get your PhD and nobody uses your code, reads your thesis code is not well documented
   
• No follow-up of your project
   
• Paper gets forgotten in the mass of papers produced
   
• You move on to the next project

How to make sure your research is sustainable?

Too many scientific papers...

• A lot of the research is incremental
• We like to stay in our comfort zone
• Taking a leap, requires time and effort and slows publication rate
• Combining things which have never been combined can often be good way forward...

Interdisciplinary research is a way to do new and exciting things no one has done before you

How can we make big leaps in science?

• Reproducible
• Sustainable
• Novel -> interdisciplinary work?

Create impact!

My scientific journey so far...

• Master degree in physics (UGent, 2004-2007)

• PhD in theoretical physics (UGent + long research stays Brazil, 2007-2001)

Phd in physics

Phd in physics

• Wanted to do applied research
• Interest in Biophysics grew when I met a newly appointed professor in my university
• Wrote and received an FWO post-doc position in a completely new field

Started computer modeling of the heart

Post-doc in computer modeling of the heart

• Research stay in Utrecht Medical center
• Wanted to check if my modeling was realistic
• Investigated experiments of a certain lethal arrhythmia called Torsade de Pointes (TdP)  in a dog model

Needle experiments

Induce TdP and investigate mechanism

preclinical research:

• in silico
• animal models

Post-doc 2: computer modeling and analysis of experiments

Had to find a new way

Started to integrate network theory to analyze the data, a whole different branch of science

It was not possible to analyze the dog data with the known methods in the literature because the data was too sparse and too noisy

Post-doc 2: computer modeling and analysis of experiments

I followed the Interdisciplinary Program in Healthcare Innovation, gave me many new insights!

Post-doc 2: computer modeling and analysis of experiments

Applied the same idea to clinical data

One year internal grant

Oct 2019: Became assistant professor UGent (Tenure Track)

Obtained ERC starting grant for 1.5 milion euros

Febr 2021: Became associate professor UGent (Permanent)

Start of Professorship

Cardiac arrhythmia: some basics

Cardiac arrhythmia: 15% - 20% of all deaths

How does the heart work

Basis of cardiac arrhythmia

Treatment cardiac arrhythmia

Ablation: scarring of tissue to stop the arrhythmia

Treatment cardiac arrhythmia

Types of arrhythmia

Atrial fibrillation

Torsade de Pointes

Regular

Irregular

Atrial tachycardia

Ventricular tachycardia

Ventricular fibrillation

Atria

Ventricles

Atrial tachycardia

Measurements give rise to a color map.

Needs to be interpreted manually: challenging and operator dependent.

Local activation time

Atrial tachycardia: case study

Looks like typical case of flutter?

Network theory as a new way to analyze cardiac arrhythmia

Search algorithm

Facebook

Brain

Network theory has many applications...

Novel idea

Rotating electrical waves are just the cycles in our network!

DGM actually works on patient data

Directed Graph Mapping

Tool that can analyze electro-anatomical mapping data using network theory

www.dgmapping.com

Directed Graph Mapping: features

www.dgmapping.com

• Input:
  • OpenCARP
  • RHYTHMIA
  • CARTO
  • Optical mapping data                                            
• Calculation:
  • Pre-processing
  • Many different phase mapping methods
  • Graph methods and measures
  • Reentry loops
  • Post-processing
• Visualization:
  • Extended toolkit for visualization
• Endlessly adaptable

Many examples!

Full Documentation

Tutorials

Directed Graph Mapping

New version almost ready open source/source available with restrictions for commercial use

You can create your own pipeline!

www.dgmapping.com

Topology added to the mix

MV

LPV

RPV

Anatomy of the left atrium: 3 natural holes

MV

LPV

RPV

Anatomy of the left and right atrium

SVC

IVC

TV

MV

LPV

RPV

Scar creates additional holes

Index theorem (> 20 years old!)

• Each hole has an index: +1, -1 or 0
   
• Sum of the indexes has to be zero

Simulation on spheres with 3 holes (or any number of holes!)

Ablation: connect the critical boundaries

CB:

CB:

NCB: 0

Outcomes

Outcomes

AstraZeneca Award for innovation

Types of arrhythmia

Atrial fibrillation

Torsade de Pointes

Regular

Irregular

Atrial tachycardia

Ventricular tachycardia

Ventricular fibrillation

Atria

Ventricles

3D structures: intermural scars

Similar as in AT!

3D structures: intermural scars

Similar as in AT!

3D structures: epi-epi or endo-endo scars

Index theorem valid on each layer,

increased complexity possible!

3D structures: intramural

Index theorem valid on each layer,

increased complexity possible!

Types of arrhythmia

Atrial fibrillation

Torsade de Pointes

Regular

Irregular

Atrial tachycardia

Ventricular tachycardia

Ventricular fibrillation

Atria

Ventricles

• Reproducible
• Sustainable
• Novel -> interdisciplinary work?

Create impact!

Some difficulties with interdisciplinary research:

• You have to learn to speak with other fields
• Medical doctors:
  different language: different words for the same thing: different ontologies
  takes time -> willing to invest this time
  share data - privacy issues (GDPR)
                    - material transfer agreements (MTAs)
• Network specialists:
  again other language, invest time in learning new subject
• You have to adapt your style to the journal, grant panel of choice (ERC)
• Explain things simple: consortium partners understand
• Listen to what the doctors want, develop your method for them (their patients), not for yourself

What did I learn?